Patients who undergo chemical therapy for cancer, who receive organ implants, or who have HIV or AIDS are at a great risk of fungal infection, mostly with opportunistic pathogens, such as Candida spp., Aspergillus spp. and Cryptococcus neoformans. The antifungals available in the market suffer with drawbacks such as toxicity and narrow spectrum of activity. As patients who become “immunocompromised” are currently increasing in number and contract serious fungal infections, there is an increasing demand for antifungal agents that have excellent inherent pharmacokinetic characteristics and potent inhibitory activities against a broad range of fungi.
A number of derivatives having antifungal activity is known and has been developed for the treatment of mammals, including humans, infected with fungi. For example, orally administrable triazole derivatives were reported in the late 1980s, and are represented by Fluconazole (UK Pat. No. 2099818), Itraconazole (U.S. Pat. No. 4,267,179) and particularly, Voriconazole (EU Pat. No. 0440372). None of them, however, show remarkable inhibitory activity against some of the opportunistic fungi which cause fatal infections in patients having decreased immunity.
Many of the antifungal agents which have been developed or are now under study are found to have additional heterocyclic substituents in addition to triazole. For instance, fluconazole has five-membered heterocyclic ring, while a six-membered heterocyclic ring is contained in voriconazole. In addition, isoxazole (EU Pat. No. 0241232, Shionogi Co.) and triazolone (EU Pat. No. 0659751, Takeda Co.) have respectively five-membered heterocyclic rings. In addition, bicyclic heterogroups are found in quinazolinone (Korean Pat. Laid-Open Publication No. 2002-0075809, Uriach Co.), quinoline (Korean Pat. Laid-Open Publication No. 1996-7003895, Fujisawa Co.), benzotriazole (U.S. Pat. No. 5,648,372, Eisai Co), benzimidazole (Chinese Pat. No. 1081189), and indole (US Pat. Publication No. 2004/67998).